The purpose of these investigations is to define the biologic parameters of normal lymphoid differentiation, beginning with multipotent stem cells and ending with highly diverse effector cells that mediate immune defense. Integrated studies of lymphoid malignancies in man and in animals will be the other major focus. Using selected animal models and organ and cell culture techniques, we will study the primary development of B lymphocytes from stem cells and, employing purified T lymphocytes, macrophages, and B lymphocytes, the requirements for terminal plasma cell differentiation in response to antigens or mitogens. B-lymphoma cells will be compared to normal B lymphocytes at different stages of differentiation in regard to the mobility of cell membrane receptors and the potential role of surface immunoglobulins in regulating the rate of cell division. The model systems will be avian lymphoid leukosis and selected human lymphomas and leukemias. Through previous work we have developed methods for selective interference with B cell differentiation in chickens and mice. These methods will be used for studies of T-cell tolerance, tumor rejection and the nature and function of primary (native) and secondary (immunoglobulin) T-cell receptors. Concanavalin A receptors on normal and malignant T and B cells will be isolated, characterized and used to raise heterologous antisera; these and other markers will be employed in characterizing lymphoid malignancies in man, concentrating first on acute lymphocytic leukemia in children. Immunodeficient mice and patients will provide sources of cells for studies on the nature of K cells and their cytolytic functions. Serum levels of alternate complement pathway factors will be correlated with splenectomy and the extent of malignancy in patients with Hodgkin's disease. Finally, methods and concepts developed from studies of lymphoreticular differentiation will be applied directly to studies on the nature of human lymphoreticular malignancies and of host-defense defects that result from cancer.